The main purpose of the proposed work is to investigate the possible role of two oncogenes in the development and maintenance of neoplasia in human\B lineage tumors, with emphasis on pre-B lymphoblastic leukemias. These oncogenes are the transforming gene (abl) found in Abelson murine leukemia virus (A-MuLV) and the transforming gene in DNA from human pre-B leukemias identified by Lane and co-workers. We term the latter gene pbt. We have identified an unusual human pre-B ALL (SMS-SB) in which both these genes appear to be activated. The anatomic presentation of this tumor and its phenotype are both strikingly reminiscent of Abelson lymphosarcoma in BALB/c mice. SMS-SB cells contain an unusually large amount of poly A RNA related to abl, including larger transcripts that are not found in normal cells or in related tumors. DNA from SMS-SB cells transfects NIH-3T3 fibroblasts at high efficiency. Based on these findings, we propose to clone the pbt gene. The cloning of the pbt gene is still in progress. The organization of the methylation pattern of the c-abl gene in SMS-SB cells and other human leukemias reveals that the gene is hypomethylated specifically in B-cell lineage tumors while other oncogenes, such as c-myc or c-myb, are not. We adapted the SMS-SB cells to grow in a serum-free media. Using this media, we demonstrated that SMS-SB cells secrete a 20 to 30 kilodalton peptide growth factor which is required for SMS-SB cells to grow at low cell density. We also found that other pre-B cell leukemias secrete a similar factor. We are currently purifying this factor and determining its relationship to known interleukins. (M)